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Biomedical subjects

P Liu

Publications and source records attributed to P Liu.

At least 73 records · Page 4Linked to original sources

Effect of food on the pharmacokinetics of a single oral dose of moxifloxacin 400mg in healthy male volunteers.

OBJECTIVE: To investigate the effects of concomitant food intake on the pharmacokinetics of a single oral dose of moxifloxacin 400mg. DESIGN: This was a randomised 2-way nonblinded crossover study in healthy volunteers. PARTICIPANTS: 18 young, healthy, male volunteers were enrolled in the study, of whom 16 were considered evaluable for the pharmacokinetic analysis. METHODS: Moxifloxacin was given under 2 conditions separated by a 1-week washout period: fasted and fed (immediately after a standardised high fat breakfast). Concentrations of moxifloxacin in serum were determined by a validated high performance liquid chromatography procedure with fluorescence detection. OUTCOME MEASURES: Pharmacokinetic parameters such as maximum concentration (Cmax), time to reach Cmax (tmax), area under the concentration-time curve from zero to 48 hours (AUC48h), AUC from zero extrapolated to infinity (AUCinfinity) and elimination half-life (t1/2z) were estimated using noncompartmental methods. The natural logarithms of AUC and Cmax were analysed using analysis of variance. Bioequivalence of the 2 treatments was determined at the 5% significance level with the two 1-sided tests procedure and limits of 80% and 125% for AUC and 70 to 143% for Cmax. RESULTS: The mean serum concentration versus time profiles were similar between the 2 treatments. The geometric mean AUCinfinity values under fed and fasted conditions were almost identical, 37.7 versus 38.5 mg/L x h, respectively [90% confidence interval (CI) of the ratio of fed versus fasted based on geometric least-square means was 0.95, 1.00]. Geometric mean Cmax values were slightly reduced by food, 2.5 versus 2.8 mg/L, respectively (90% CI of fed versus fasted based on geometric least-square means was 0.78, 0.98). The absorption of moxifloxacin seems to be mildly delayed because of the effect of food; the median tmax values were 1.0 and 2.5 hours for fasted and fed conditions, respectively. The single oral dose of moxifloxacin 400mg was well tolerated when taken with and without food.

Administration, Oral↗

[Genetic polymorphisms of cytochrome P450 1A1 and susceptibility of early-onset Parkinson's disease].

OBJECTIVE: To assess the possible association between the Msp I polymorphisms of cytochrome P450 1A1(CYP1A1) and the susceptibility of early-onset Parkinson's disease among Hans in the northern part of China. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to analyze three genotypes A, B and C in 3'flanking region of CYP1A1 in 126 patients with idiopathic early-onset Parkinson's disease and 172 healthy controls. RESULTS: The frequencies of genotypes A, B and C in patients were 41.3%, 43.6% and 15.1% while those in the controls were 34.9%, 51.7% and 13.4%, respectively. No statistically significant difference in the frequencies of the three genotypes was observed between the two groups. The frequencies of two alleles were of no significant difference between the patients and controls. CONCLUSION: The above results suggest that the Msp I polymorphisms of cytochrome P450 1A1 itself might not be associated with idiopathic early-onset Parkinson's disease.

Adult↗

[Changes of lipid peroxidation in liver fibrogenesis induced by dimethylnitrosamine and drugs' intervention].

OBJECTIVE: To investigate the pathological actions of lipid peroxidation implicated in liver fibrogenesis induced by dimethylnitrosamine (DMN), and the mechanism of Fuzheng Huayu 319 decoction (319 decoction) and interferon-gamma (IFN-gamma) actions against liver fibrosis. METHODS: A liver fibrotic model was induced by intraperitoneal injection of DMN in rats, and treated with 319 decoction and IFN-gamma, respectively. The liver sections were stained with HE and ponceau for collagens, and the liver functions were assayed. The contents of hepatic hydroxyproline (Hyp) and malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) were measured. The correlation among SOD, MDA and Hyp was analyzed. RESULTS: In the models, hepatic collagens proliferated remarkably and fibrous septa were formed. Serum ALT activities increased. Both Hyp and MDA enhanced obviously, but SOD decreased markedly. SOD was significantly negatively correlated with MDA and Hyp, respectively (r=-0.70, -0.73, P<0.01), and MDA was significantly positively correlated with Hyp (r=0.88, P<0.01). While both 319 decoction and IFN-gamma attenuated collagen proliferation and deposition, decreased ALT level, increased SOD activity, but decreased MDA and Hyp contents. CONCLUSIONS: DMN can cause hepatic lipid peroxidation, which is closely involved in liver fibrogenesis induced by DMN. The effect against hepatic lipid peroxidation is one of the important mechanisms of 319 decoction and IFN-gamma actions against liver fibrosis.

Animals↗

[Intervention of Fuzhenghuayu decoction on autocrine activation of hepatic stellate cells].

OBJECTIVE: To investigate the intervention of Fuzhenghuayu decoction on autocrine activation of hepatic stellate cell. METHODS: The drug serum containing Fuzhenghuayu decoction was collected from the normal rats, and cultured with activated hepatic stellate cells (HSC) in vitro. The conditional medium from the drug serum treated HSC was collected, and added to primarily cultured quiescent HSC. The primary cell proliferation was assayed by MTT colorometric test, and the contents of type I collagen and vasular endothelial growth factor (VEGF) in the medium were assayed with ELISA. RESULTS: The coditional medium from activated HSC could stimulate the proliferation and type I collagen secretion in the quiescent HSC. The drug serum inhibited this stimulating action and VEGF secretion from activated HSC. CONCLUSIONS: Fuzhenghuayu decoction has inhibitory action on the autocrine-activating pathway of HSC. The mechanism may be associated with inhibiting the secretion of VEGF by activated HSC.

Animals↗

Brain natriuretic peptide: is it a predictor of cardiomyopathy in cirrhosis?

Subtle cardiac abnormalities have been described in patients with cirrhosis. Natriuretic peptide hormones have been reported to be sensitive markers of early cardiac disease. We postulate that plasma levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide could be used as markers of cardiac dysfunction in cirrhosis. The aim of the study was to evaluate the levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide and their relationship with cardiac structure and function in patients with cirrhosis. The study population comprised 36 patients with cirrhosis of mixed aetiologies, but with no cardiac symptoms; 19 of the patients had ascites and 17 did not. The subjects underwent (i) trans-thoracic two-dimensional echocardiography, and (ii) radionuclide angiography for measurements of cardiac structural parameters, diastolic and systolic function. Levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide were also measured. The results were compared with those from eight age- and sex-matched healthy volunteers. Compared with the controls, the baseline mean ejection fraction was increased significantly in both patient groups (P=0.02), together with prolonged deceleration times (P=0.03), left atrial enlargement (P=0.03) and interventricular septal thickening (P=0.02), findings that are compatible with diastolic dysfunction. Levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide were significantly higher in all patients with cirrhosis with ascites (P=0.01 and P=0.05 respectively), but in only some of the pre-ascitic cirrhotic patients, compared with controls. All high levels of brain natriuretic peptide were correlated significantly with septal thickness (P<0.01), left ventricular diameter at the end of diastole (P=0.02) and deceleration time (P<0.01). We conclude that elevated levels of brain natriuretic peptide are related to interventricular septal thickness and the impairment of diastolic function in asymptomatic patients with cirrhosis. Levels of brain natriuretic peptide may prove to be useful as a marker for screening patients with cirrhosis for the presence of cirrhotic cardiomyopathy, and thereby identifying such patients for further investigations.

Adult↗

[Role of vascular endothelial growth factor in the genesis of pregnancy induced hypertension and its relationship with nitric oxide].

OBJECTIVE: To study the role of vascular endothelial growth factor in the genesis of pregnancy induced hypertension (PIH) and its relationship with nitric oxide. METHODS: Serum vascular endothelial growth factor(VEGF) levels in 41 women with PIH and 20 normal pregnant women were measured by enzyme linked immunosorbent assay. The concentrations of nitric oxide (NO) in placental tissues were assayed by nitrite reductase. RESULTS: (1) Serum levels of vascular endothelial growth factor VEGF in PIH group were significantly lower than those in normal pregnancy. There was no difference between the mild PIH and normal group in the concentrations of VEGF. VEGF levels in moderate (23.1 +/- 4.1) ng/L and severe PIH (14.8 +/- 3.9) ng/L were significantly lower than those in normal group (P < 0.01). (2) The concentrations of NO in placental tissues in PIH group were significantly lower than those in normal pregnancy (P < 0.01). There was no difference between the concentrations of NO in mild PIH and those in normal pregnancy (P > 0.05). NO levels in moderate PIH (9.1 +/- 2.1) mumol/g and severe PIH (5.6 +/- 1.8) mumol/g were significantly lower than those in control group. (3) The serum levels of VEGF positively correlated with the concentration of NO in placental tissues. (r = 0.65, P < 0.01). CONCLUSION: The serum levels of VEGF and the concentrations of NO in women with PIH are both suppressed. The changes of VEGF levels might play an important role in the pathogenesis of PIH.

Endothelial Growth Factors↗

[Study of telomerase activity and its related genes expression in leukemia cells].

OBJECTIVE: To investigate the changes of telomerase activity and its related genes expression in leukemia cells and their roles in leukemogenesis. METHODS: The telomerase activity in bone marrow cells of 47 leukemia patients were detected by a semi-quantitative telomeric repeat amplification protocol (TRAP)-silver staining, and the expression of telomerase related genes hEST2, TP1 and hTR by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: The telomerase activity and expression of telomerase related genes were significantly higher in 42 leukemia patients in progress stage than that in complete remission/chronic stage and in normal/anemia cases (P < 0.01). The telomerase activity and expression of TP1, hTR gene in 14 cases of acute leukemia complete remission (AL-CR)/chronic myelogenous (CML)-chronic stage were higher than that in normal/anemia cases (P < 0.05). Low levels of telomerase activity and telomerase related genes expression could be detected in part of normal bone marrow cells. The levels of telomerase activity and telomerase related genes expression in 3 cases of anemia increased after short-term culture. CONCLUSIONS: High level of telomerase activity and its related genes expression were specific markers of malignant hematopoietic cells and their changes might be useful for observation of treatment effectiveness in leukemia. Low level of telomerase activity was associated with hematopoietic stem cells with the ability of proliferation. hEST2 gene might be a up-regulation gene of telomerase; hTR might be related to feedback regulation of telomerase.

Adolescent↗

[Pathological and virological studies of the liver tissues from the patients with sporadic hepatitis E].

OBJECTIVE: To study the pathological feature, viral distribution and replication in the liver tissue of sporadic hepatitis E(HE), and to explore the mechanism of the liver injury induced by hepatitis E virus(HEV). METHODS: The total bioptic liver tissues (n=54) were obtained from the patients with sporadic hepatitis E, including the clinical acute stage (n=20), the convalescent stage (n=16), and the chronic hepatitis B (CHB) overlapped with HEV infection recently (n=18). The pathological changes in the liver tissues were observed under the light and the electron microscope. HEV RNA was detected by in situ hybridization, and Kupffer cells were marked with immunohistochemistry. RESULTS: The HE liver tissues showed the pathological features in the clinical acute stage, presenting frequently with feathery degeneration of hepatocytes (100%), cholangiolar cholestasis (75.0%), and double nuclei and multinuclei hepatocytes (65.0%). The apoptotic body of hepatocyte was larger and irregular, and the proliferation of Kupffer cells was prominent. HEV RNA was distributed in hepatocyte cytoplasm near the nuclei. The positive rate of HEV RNA in acute stage was evidently higher than that in convalescent stage (100% vs 12.5%,P < 0.001), and the HEV RNA positive hepatocytes and the viral copies in acute stage were also more than in convalescent stage, in which the liver tissues were becoming normal. The liver tissue changes of the CBH overlapped with HEV infection were more severe compared with the single CHB. CONCLUSIONS: Sporadic HE had histopathological characteristics. HEV infection and replication in hepatocytes occurred mainly during clinical acute stage and regressed in convalescent stage, which suggested sporadic acute HE may have a good result. The immune-mediated liver injury by lymphocytes might be a main pathogenesis of HE,but the liver injury induced directly by HEV might not be excluded.

Adolescent↗

[Comparing the two neurobehavioral toxicological methods on the toxic effect of methyl mercury].

To compare the two experimental methods for testing neurobehavioral toxicological effects, methyl mercury chloride at the dosage of 0.00, 0.01, 0.05 and 2.00 mg/(kg.d) was force-fed to pregnant Wistar rats during the 6-9th day of conception. The offspring of the 4 groups were randomly selected for Y maze or operant behavior test at the age of 7 or 10 weeks, respectively. The reinforcements of the performance were electric shock for Y maze and food pellets for operant behavioral test. The results showed that no sex-dependent effects were observed both in maze and operant behavior tests. The performances of offspring in 3 exposure groups were worse than that of control group both in Y maze and operant behavior tests(P < 0.05). It was demonstrated that a clear dose-effect relationship in maze test on error time(rs = 0.257, P < 0.05), arrival time(rs = 0.216, P < 0.01); in operant behavior test on differential reinforcement of high rate (rs = -0.7273, P < 0.01), but not on differential reinforcement of low rate(rs = -0.2238, P > 0.05). It is concluded that prenatal methyl mercury exposure caused some negative effects on the development of nervous system. But the negative reinforcement by human operation in Y maze test could affect the results. The positive reinforcement and automatic monitoring in operant behavioral test gave more reliable results.

Animals↗

[Effect of recombinant epidermal growth factor on corneal epithelial cells after excision of pterygium].

OBJECTIVE: To investigate the effects of recombinant epidermal growth factor on the wounded corneal healing after excision of pterygium. METHODS: Simple and unrecurrent pterygium was selected, excised and sewed up conjunctival flap under local anaesthesia and microscope. After operation two drops of EGF eyedrop were used, and five minutes later 0.3% Tarivid Eye Oint was used again, and then the operated eye was enswathed. Everyday the wound cornea was observed and the EGF eyedrop was used. RESULTS: The wound cornea healing time of control group was seven days and that of the EGF group was five days and gave a remarkable difference (P < 0.05). The same results were obtained after comparing the effective group and ineffective group, P < 0.05. CONCLUSIONS: EGF eyedrop can accelerate proliferation and recovery of wound corneal epithelial cells. In the clinical trial, every body felt well and no side-effect was observed.

Adolescent↗

[A clinical application and study of analysis system of sound spectrography].

OBJECTIVE: The phonetic features were studied for non-velopharyngeal dysfunction in postoperative patients with cleft plate. METHODS: The feature of velopharyngeal competency of 32 postoperative patients with cleft palate were analyzed with KAY-7800 sound spectrograph, compared with characteristic of 30 subjects with normal phonogram. RESULTS: There were three types of abnormal phonogram for the postoperative patients of cleft palate with velopharyngeal competence. The heavy noise was a common sight. CONCLUSION: An analytic system of sound spectrography has certain value for evaluation of phonic function in cleft palate patients.

English Abstract↗

Right and left ventricular systolic function late after repair of tetralogy of Fallot.

Right ventricular (RV) dysfunction has adverse effects on long-term outcome in patients with repaired tetralogy of Fallot (TOF). We employed serial radionuclide angiography (RNA) to examine RV and left ventricular (LV) systolic function in adults late after TOF repair and its relation to clinical outcome. We reviewed 10-year records of 95 patients (53 men) with TOF followed in our clinic (mean age at repair 12.6 +/- 10.5 years, mean age at last follow-up 37.7 +/- 9.8 years) who underwent at least 2 RNAs between 1987 and 1997. Most patients were well by the end of the study (80% were New York Heart Association class I, 17% were class II, and 3% were in class III). Sixteen patients experienced sustained tachyarrhythmias (8 had atrial; 8 patients had ventricular). One patient died suddenly. Fifteen patients underwent RV outflow reoperations (15 underwent pulmonary valve replacement; 7 had relief of RV outflow obstruction); RV systolic function during exercise in these 15 patients was significantly impaired before and returned to similar levels after surgery, compared with the rest of the patients. Overall, RV and LV function remained stable in the whole group at a mean interval of 5.7 +/- 2.2 years between first and last RNA. This group of closely followed adults with TOF remained well over 10 years with a low incidence of sudden death and stable RV and LV systolic function, despite a relatively large number of RV outflow reoperations. Aggressive intervention for right-sided hemodynamic abnormalities may have contributed to this outcome. Preserved ventricular function may herald a favorable long-term outlook in this group.

Adult↗

Microdialysis in peripheral tissues.

The objective of this review is to survey the recent literature regarding the applications of microdialysis in pharmacokinetic studies and facilitating many other studies in peripheral tissues such as muscle, subcutaneous adipose tissue, heart, lung, etc. It has been reported extensively that microdialysis is a useful technique for monitoring free concentrations of compounds in extracellular fluid (ECF), and it is gaining popularity in pharmacokinetic and pharmacodynamic studies, both in experimental animals and humans. The first part of this review discusses the use of microdialysis technique for ECF sampling in peripheral tissues in animal studies. The second part of the review describes the use of microdialysis for ECF sampling in peripheral tissues in human studies. Microdialysis has been applied extensively to measure both endogenous and exogenous compounds in ECF. Of particular benefit is the fact that microdialysis measures the unbound concentrations in the peripheral tissue fluid which have been shown to be responsible for the pharmacological effects. With the increasing number of applications of microdialysis, it is obvious that this method will have an important place in studying drug pharmacokinetics and pharmacodynamics.

Adipose Tissue↗

A nucleoprotein complex containing CCAAT/enhancer-binding protein beta interacts with an insulin response sequence in the insulin-like growth factor-binding protein-1 gene and contributes to insulin-regulated gene expression.

Highly related insulin response sequences (IRSs) mediate effects of insulin on the expression of multiple genes in the liver, including insulin-like growth factor binding protein-1 (IGFBP-1) and phosphoenolpyruvate carboxykinase (PEPCK). Gel shift studies reveal that oligonucleotide probes containing an IRS from the IGFBP-1 or PEPCK gene form a similar complex with hepatic nuclear proteins. Unlabeled competitors containing the IGFBP-1 or PEPCK IRS or a binding site for C/EBP proteins inhibit the formation of this complex. Antibody against C/EBPbeta (but not other C/EBP proteins) supershifts this complex, and Western blotting of affinity purified proteins confirms that C/EBPbeta is present in this complex. Studies with affinity purified and recombinant protein indicate that C/EBPbeta does not interact directly with the IRS, but that other factors are required. Gel shift assays and reporter gene studies with constructs containing point mutations within the IRS reveal that the ability to interact with factors required for the formation of this complex correlates well with the ability of insulin to regulate promoter activity via this IRS (r = 0.849, p < 0.01). Replacing the IRS in reporter gene constructs with a C/EBP-binding site (but not an HNF-3/forkhead site or cAMP response element) maintains the effect of insulin on promoter activity. Together, these findings indicate that a nucleoprotein complex containing C/EBPbeta interacts with IRSs from the IGFBP-1 and PEPCK genes in a sequence-specific fashion and may contribute to the ability of insulin to regulate gene expression.

Binding Sites↗

Estrogen receptor alpha and endothelial nitric oxide synthase are organized into a functional signaling module in caveolae.

Estrogen causes nitric oxide (NO)-dependent vasodilation due to estrogen receptor (ER) alpha-mediated, nongenomic activation of endothelial NO synthase (eNOS). The subcellular site of interaction between ERalpha and eNOS was determined in studies of isolated endothelial cell plasma membranes. Estradiol (E(2), 10(-8) mol/L) caused an increase in eNOS activity in plasma membranes in the absence of added calcium, calmodulin, or eNOS cofactors, which was blocked by ICI 182,780 and ERalpha antibody. Immunoidentification studies detected the same 67-kDa protein in endothelial cell nucleus, cytosol, and plasma membrane. Plasma membranes from COS-7 cells expressing eNOS and ERalpha displayed ER-mediated eNOS stimulation, whereas membranes from cells expressing eNOS alone or ERalpha plus a myristoylation-deficient mutant eNOS were insensitive. Fractionation of endothelial cell plasma membranes revealed ERalpha protein in caveolae, and E(2) caused stimulation of eNOS in isolated caveolae that was ER-dependent; noncaveolae membranes were insensitive. Acetylcholine and bradykinin also activated eNOS in isolated caveolae. Furthermore, the effect of E(2) on eNOS in caveolae was prevented by calcium chelation. Thus, a subpopulation of ERalpha is localized to endothelial cell caveolae where they are coupled to eNOS in a functional signaling module that may regulate the local calcium environment. The full text of this article is available at http://www.circresaha.org.

Acetylcholine↗

Purification, characterization, and cDNA sequence of halysetin, a disintegrin-like/cysteine-rich protein from the venom of Agkistrodon halys Pallas.

By means of DEAE-Sepharose CL-6B column chromatography, gel filtration on Sephadex G-75 and Superose 12 FPLC, halysetin, an antiplatelet protein, was purified from the venom of Agkistrodon halys Pallas with molecular mass of 29 kDa on SDS-PAGE and 23,168 Da by mass spectrometry. The p1 was about 5.0. Halysetin was devoid of phospholipase A2, fibrino-(geno)lytic, esterase, hemorrhagenic activities. Halysetin dose-dependently inhibited the aggregation of human platelet, which was stimulated by collagen with IC50 of 420 nM, but not that stimulated by ADP. The N-and C-terminal sequences of halysetin were characterized. Its full-length cDNA was cloned by RT-PCR from the total RNA extracted from the snake venom gland. It encoded a protein of 212-amino-acid residues with disintegrin-like/cysteine-rich domains and was highly homologous with SYMPs (snake venom metalloprotease).

Adenosine Diphosphate↗